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S Piacentini

Publications and source records attributed to S Piacentini.

51 records · Page 3Linked to original sources
PubMed1992

Free radical injury in skin cultured fibroblasts from Alzheimer's disease patients.

Oxygen radical production is postulated to be a major cause of cell damage in aging. We have studied the response to toxic oxygen metabolites of fibroblast cell lines derived from skin biopsies of patients with familial and sporadic Alzheimer's disease compared with those derived from normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 mU of xanthine-oxidase. To quantify cell damage we measured lactate dehydrogenase activity in the culture medium and cell viability in fibroblast cultures from four normal subjects, five FAD, and four AD patients after 2 hours of Xo incubation. We found a significant increase of LDH activity in FAD vs. controls and also in AD vs. controls, suggesting that AD cells are more susceptible to oxygen radical damage than are normal controls.

Alzheimer Disease↗
PubMed1992

Alzheimer skin fibroblasts show increased susceptibility to free radicals.

We have studied the response to toxic oxygen metabolites of fibroblasts derived from skin biopsies of 5 patients with familial (FAD) and 4 with sporadic (AD) Alzheimer's disease compared with those derived from 4 normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 munits of xanthine-oxidase (Xo). To quantify cell damage we measured lactate dehydrogenase (LDH) activity in the culture medium and cell viability in fibroblast cultures. We found a significant increase in LDH activity in the FAD vs. controls and also in the AD vs. controls.

Acetaldehyde↗
PubMed1992

Clinical evaluation of oral fluid samples for diagnosis of viral hepatitis.

Oral fluid samples were compared with serum samples as a specimen source for hepatitis A, B, and C virus markers. Oral fluid was obtained with a treated absorbent pad and tested by using existing commercial enzyme immunoassays with only minor modifications. Compared with serum sampling the sensitivity and specificity of oral sampling were 100% (51 of 51 samples) and 98% (46 of 47 samples) for hepatitis A virus immunoglobulin M, 100% (29 of 29 samples) and 100% (29 of 29 samples) for hepatitis B virus surface antigen, and 100% (13 of 13 samples) and 100% (13 of 13 samples) for hepatitis C virus antibody, respectively. The decline of hepatitis A virus immunoglobulin M in oral samples was parallel to, though somewhat more rapid than, that of hepatitis A virus immunoglobulin M in serum samples. It is proposed that oral sampling represents a safer and more convenient procedure for reliable hepatitis virus testing than blood sampling and that it has wide application in patient and outbreak management.

Antibodies, Viral↗
PubMed1991

The first Alzheimer disease case: a metachromatic leukodystrophy?

A reconsideration of the original report of Alzheimer and of the description of case 1 by Perusini in 1908, published in 1910, suggests that they were describing the same case. Both the temporal evidence and the clinical description make this conclusion inescapable. The histopathology of this first case shows some features that are not characteristic of the histological pattern of the modern Alzheimer, namely demyelination of the central white matter and metachromatic deposits in the spinal cord.

Alzheimer Disease↗
PubMed1990

Occurrence of transketolase abnormalities in extracts of foreskin fibroblasts from patients with Alzheimer's disease.

Foreskin fibroblast cell lines from healthy subjects and patients with Alzheimer's disease or other neurological disorders have been analyzed for transketolase, by means of isoelectrofocusing and specific immunostaining. The enzyme profile in 70% of Alzheimer cell cultures exhibits alterations which are not encountered in controls and in other neurological diseases examined. Enzyme abnormalities most frequently observed were the appearance of new transketolase forms having unusually high alkaline pI. Experiments carried out with intact cells and with cell extracts treated with and without phenylmethyl-sulphonyl fluoride, suggest that the peculiar transketolase abnormalities observed in Alzheimer fibroblasts are due to enhanced proteolysis occurring in these cells rather than to intrinsic enzyme lability.

Alzheimer Disease↗
PubMed1990

Altered hexokinase activity in skin cultured fibroblasts and leukocytes from Alzheimer's disease patients.

Changes in the activity of brain glycolytic enzymes have been reported in Alzheimer's dementia. In this paper we studied the activity of the rate-limiting glycolytic enzymes, namely phosphofructokinase, lactate dehydrogenase and hexokinase in skin cultured fibroblasts and leukocytes from familial and sporadic Alzheimer's disease patients and unaffected relatives. Phosphofructokinase and lactate dehydrogenase activities were similar in all groups studied. The activity of hexokinase was reduced in some patients with the familial dominant form of Alzheimer's disease whilst it was normal in sporadic cases. These results suggest that Alzheimer's disease may be an heterogeneous disorder and that a modification on the catalytic activity of hexokinase may play a role in the pathogenesis of the disease in at least a subgroup of patients.

Alzheimer Disease↗
PubMed1989

Abnormalities of mitochondrial enzymes in hereditary ataxias.

The activity of 7 mitochondrial enzymes, fumarase, NAD-malate dehydrogenase (MDH), citrate synthase (CS), valine dehydrogenase (VDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), pyruvate dehydrogenase complex (PDHC) has been measured in platelet preparations from patients affected by Friedreich's ataxia (FA), dominant and non-dominant olivopontocerebellar atrophy (DOPCA, NDOPCA) and normal individuals. Significant decreases of GDH (P less than 0.01), PDHC (P less than 0.01), VDH (P less than 0.05) and SDH (P less than 0.05) activities were observed in FA patients. Significant decreases of GDH (P less than 0.01), PDHC (P less than 0.01), VDH (P less than 0.05), SDH (P less than 0.05) and CS (P less than 0.05) activities were Observed in ND-OPCA patients, whereas in DOPCA patients only GDH activity was significantly (P less than 0.05) decreased. In 8 of 10 patients with FA and in all patients with NDOPCA the activity of one or more of 4 enzymes, i.e. GDH, VDH, SDH, PDHC, was lower than the lowest of control values. Four of 6 patients with DOPCA had GDH activity lower than the lowest of control values. These results indicate that abnormalities of mitochondrial metabolism is a constant element in hereditary ataxia and suggest that the alteration primary leading to the different types of ataxias should be related to mitochondrial oxidative metabolism, at least at a regulatory level.

Adolescent↗
PubMed1988

Lack of efficacy of phosphatidylcholine in ataxias.

We gave phosphatidylcholine orally at a daily dosage of 9 grams for 4 years to 20 subjects with Friedreich's ataxia (FA) and 24 with olivopontocerebellar atrophy (OPCA). There was no clinical improvement during the follow-up compared with 12 ataxic patients (six FA and six OPCA) who did not receive any treatment. A 6-month trial at a double dose did not have any significant effect. This study indicates that phosphatidylcholine does not change the natural course of ataxias.

Ataxia↗
PubMed1987

Intralaminar distribution of neurotransmitter-related enzymes in cerebral cortex of Alzheimer's disease.

The intralaminar distribution of choline acetyltransferase, galactocerebrosides, gangliosides and proteins were determined in frontal (Brodmann's area 9) and temporal (Brodmann's area 22) cortices from subjects with autopsy-proven Alzheimer's disease and controls matched for sex, age and postmortem delay. In normal brain choline acetyltransferase (CAT) activity was higher in the II and IV layers in the temporal cortex, while in frontal cortex CAT activity was relatively high in the II-III layer, appearing as a single peak. The intracortical distribution of galactocerebrosides normally shows a trend to a higher activity from the pial surface to white matter either in frontal or temporal cortices. Higher concentrations of gangliosides were associated with the cell body layers in either frontal or temporal cortices. In either frontal and temporal cortices from 5 patients with Alzheimer's disease the pattern of intralaminar distribution of CAT activity was completely disrupted and it was significantly lower than in all cortical layers of the controls. Galactocerebrosides concentration was significantly decreased in the lower layers (IV, V and VI) in both frontal and temporal cortices and ganglioside sialic acid concentration was also decreased in the Alzheimer brain consistently in the lower (III-IV) layers of the frontal and temporal cortices. These observations indicate a widespread involvement of cholinergic activities through all cortical layers. However, the selective decrease in galactocerebroside concentration in the lower layers (IV-VI) suggests a selective loss of ascending fibers from subcortical nuclei. The decreased concentration of ganglioside sialic acid in lower layers suggests a selective axodendritic degeneration in these laminae of frontal association and temporal cortex in Alzheimer's disease.

Aged↗
PubMed1986

Abnormal platelet glutamate dehydrogenase activity and activation in dominant and nondominant olivopontocerebellar atrophy.

Glutamate dehydrogenase (GDH) activity and its allosteric modulation by purine nucleotides were studied in platelet preparations from 4 patients with a nondominant form of adult-onset olivopontocerebellar atrophy (OPCA) and in affected and nonaffected members of two families with a dominant form of OPCA. A partial deficiency of GDH activity (40 to 50% of control values) was present in 3 patients with nondominant OPCA and in 2 patients, father and son, with a dominant form of OPCA. Platelet GDH from these patients and controls was regularly inactivated by 2 mM guanosine-5'-triphosphate (GTP) and simulated one- to twofold by 2 mM adenosine-5'-diphosphate (ADP). In the presence of 0.2% Triton X-100, the activating effect of ADP was enhanced four- to sixfold. The partial deficiency in maximum catalytic activity observed in these patients persisted under all conditions used for enzyme assay. In affected members, but not in one unaffected member of another family with a dominant type of OPCA, GDH activity was in the control range but was not activated by ADP in either the presence or absence of Triton. These results suggest that there may be at least two possible alterations of GDH in patients with OPCA: one which decreases the maximum catalytic activity and one which impairs the regulatory properties of the enzyme. Furthermore, this study suggests that platelet GDH determination in patients with OPCA may provide a simple and useful tool to classify these disorders and to understand the basic pathophysiological mechanisms involved.

Adolescent↗
PubMed1986

Energy metabolism in demented brain.

The term dementia refers to a number of very complicated disorders of the brain with several morphological, biochemical and functional alterations. Several alterations occur in Alzheimer's disease. They include alteration in neurotransmitters related substances and changes in brain metabolic rate. Changes in metabolic activity are among the earliest and best documented of all modification reported in Alzheimer's brain. They appear to be correlate with the severity of the disease, and to be more marked in specific areas of the brain which appear to be clinically more involved. In this report will be discussed the observations on changes of cerebral glucose metabolic rate, cerebral oxygen consumption, cerebral blood flow reported in vivo in demented patients. The observations of changes in energy metabolism related enzymes and the relationship between these changes and those in neurotransmitters related substances will be also reviewed.

Alzheimer Disease↗
PubMed1982

Kinetic studies of mouse brain transketolase.

The activity of transketolase in mouse brain was 5.7 nmol/min/mg protein measured by an enzyme-coupled spectrophotometric assay. The apparent Km for ribose-5-phosphate was 330 microM, for D-xylulose-5-phosphate was 120 microM, and for thiamine pyrophosphate was 7 microM. However, thiamine pyrophosphate remained tightly bound to transketolase in homogenates in which it dissociated completely from another thiamine pyrophosphate-dependent enzyme, the pyruvate dehydrogenase complex. These data suggest that loss of transketolase activity is likely to be a later consequence of thiamine deficiency in mammalian brain than is decreased activity of pyruvate dehydrogenase complex.

Animals↗
PubMedDate not supplied

Clinical and genetic analysis of hereditary and sporadic ataxia in central Italy.

We have clinically and genetically evaluated 24 affected patients belonging to 22 Italian Friedreich ataxia (FA) families, 52 patients from 32 kindreds with proven autosomal dominant cerebellar ataxia (ADCA), 9 patients belonging to 5 families with autosomal recessive hereditary ataxia (ARCA) and 103 sporadic cases, 89 of which affected by idiopathic late onset cerebellar ataxia (ILOCA). Genotype-phenotype correlation analyses in FA patients have evidenced an inverse relationship between GAA repeat expansion length and age of onset, disease duration, and presence of cardiomyopathy. Among autosomal dominant types, spinocerebellar ataxia 2 (SCA2) genotype has been found in 31% of our ADCA families, resulting the most frequent form of ataxia. Phenotypic analysis of the various SCA subtypes evidenced a marked heterogeneity of symptoms with a substantial overlap between different syndromes.

Adult↗
PubMedDate not supplied

Double-blind, crossover, placebo-controlled clinical trial with L-acetylcarnitine in patients with degenerative cerebellar ataxia.

Despite the different genetic defects underlying degenerative ataxias, it has been suggested that mitochondrial energy production and antioxidative metabolism dysfunction may be common biochemical alterations related to these diseases. Acetylcarnitine, a cholinomimetic substance, is involved in oxidative metabolism and is a potential source of acetyl groups for the synthesis of acetylcholine in the mammalian brain. To determine whether treatment with L-acetylcarnitine may improve some clinical conditions of patients with ataxia, a double-blind crossover study with L-acetylcarnitine was performed in 24 patients with degenerative cerebellar diseases. Patients were selected from an ongoing prospective follow-up study at the Department of Neurology at the University of Florence, Italy. Each treatment phase with L-acetylcarnitine or placebo lasted 6 months, after which patients were crossed over to the other treatment phase. Ataxia was documented and quantified with use of a clinical score. After the trial, we observed a statistically significant improvement of some symptoms and a slow progression of the disease in both groups of patients.

Acetylcarnitine↗